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Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22721-22729. doi: 10.1073/pnas.1904396116. Epub 2019 Oct 21.

Polymerase III transcription is necessary for T cell priming by dendritic cells.

Author information

1
Aix Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy (CIML), 13288 Marseille Cedex 9, France.
2
Institute for Research in Biomedicine, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.
3
CNRS "Mistra," International Associated Laboratory, 13288 Marseille Cedex 9, France.
4
Institute for Biochemistry and Molecular Biology, University of Hamburg, 21046 Hamburg, Germany.
5
Aix Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy (CIML), 13288 Marseille Cedex 9, France; gatti@ciml.univ-mrs.fr pierre@ciml.univ-mrs.fr.
6
Ilidio Pinho Foundation, 4150-146 Porto, Portugal.

Abstract

Exposure to microbe-associated molecular patterns (MAMPs) causes dendritic cells (DCs) to undergo a remarkable activation process characterized by changes in key biochemical mechanisms. These enhance antigen processing and presentation, as well as strengthen DC capacity to stimulate naïve T cell proliferation. Here, we show that in response to the MAMPS lipopolysaccharide and polyriboinosinic:polyribocytidylic acid (Poly I:C), RNA polymerase III (Pol lII)-dependent transcription and consequently tRNA gene expression are strongly induced in DCs. This is in part caused by the phosphorylation and nuclear export of MAF1 homolog negative regulator of Poll III (MAF1), via a synergistic casein kinase 2 (CK2)- and mammalian target of rapamycin-dependent signaling cascade downstream of Toll-like receptors (TLRs). De novo tRNA expression is necessary to augment protein synthesis and compensate for tRNA degradation driven by TLR-dependent DC exposure to type-I IFN. Although protein synthesis is not strongly inhibited in absence of RNA Pol III activity, it compromises the translation of key DC mRNAs, like those coding for costimulatory molecules and proinflammatory cytokines, which instead can be stored in stress granules, as shown for CD86 mRNA. TLR-dependent CK2 stimulation and subsequent RNA Pol III activation are therefore key for the acquisition by DCs of their unique T cell immune-stimulatory functions.

KEYWORDS:

CD86; casein kinase 2; immunity; interferon; protein synthesis

PMID:
31636192
PMCID:
PMC6842613
[Available on 2020-04-21]
DOI:
10.1073/pnas.1904396116

Conflict of interest statement

The authors declare no competing interest.

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